~T·: british-American Tobacco Company Limited TECHNOLOGY CENTRE PO Box 90 RlgantJ Park Road Soukmpton SOg'lFS England felaphOna: Southampton IOt031 782111 Telex: 47289 Fax: 107031 779715 21 May 1992 RRBIBtMIRepons See Distribution Report No,t.24~ The Effect on Imnact. Irritatian_an~Mouthful of Addition. ofG1Ycarol or Hexadecans to Floe~cured~e~ParatteJ The title of this report is seltaxplanatory. The two compounds selected for the work represent water soluble and water insoluble substances and were potential means of altering the distribution of nicotine between the particulate and vapour phases of smoke, Some differences in the mouthful sensation were observed, I;~EIBJI~ R,R, Baker Distribution Dr, P,J, Dunn, Tn, Canada Prot, E, Rittershaus, BA'TCF, Germany Mr, E, Grant, Argentina Dr, C,J,P, de Sipueira, Scuta Cna Dr, E, Kausch, BA'ICF, Germany Mr, A,G, Stephenson, BTe, Southampton Dr, S,R, Massey, ITL, Canada Mr, H,V, Thomsen, Denmark Mr, G,A, Read, Millbank Dr, J,S, Wigand, B~W, USA Mr, t,l, Wilson, Australia End, t LLeo OllKI MIUlllli KIYIYLIQUW SIIIIIW TW)I )DY A Mu~ w tnl IIAT Inwmm Glw,lwewluno It lanwn No IIW1 C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 .zul FI1E NO: REPORTTYPE (RD orT): ( (DeteoPiued by Issuer) PROJECT NO: REPORT NO: Securily ClwsiT~a~on: @M~cd by Issuer) ~i~e REPORT TITLE: ~ji~CT J)~I~~J ·';e Pc ~x.J)F(~4 ~1 ~A(uvrt"l O~mll~ ~h~EkliSt l·C· Fik~;ropb I No: (To Drawing Office) rinaa: c.J SkfPJ FidCrop~· No: (Compotcrhown) CO~VIOW~ERS: Pbotognp~·No: SECI1ON IEADeRntEVIEWER: e~A~ tssvnu: J? rL~ Dls~R~sunON: RE (1): ALH(l): M1R(2): PID(I): SRM(1): TIW(2): FR(1): ~(1): CJPdeS(l): INT(1): RFG(I): Libruy(2): Pile DISK REFEREN~E: TIPPJG I~ CHECRPRi SiePa~re I I~Fe Seat I Dfte Ihte Autbod Dste Issuer Date Re#ived I Rcwned I Rmkewrr Drdtfor I I ~ ~· S·rZ Typing 1~/188 Iricl 11113-5-gz Corne~b~ ;ilik~ Papan One Bclmd CoW Issue I IA~~h J21q Thirproformo is intended lofaciliuue and dmdl the p~ogrws of BATU~RE R~D Cenae Rlportsj~am the b rlpL~c~p~ stage until the report isFMUy Ilppoovd and issued TF~proforr~ should he commmced at the G thne of the initial typing and acrompcury ~II rlpescript land r~st~ oftn preporation) at all subsegumt n; stog# h mua he mt to CenttalRecords with the Mosta when the report is trs~d, Irl Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 THE EFFECT ON IMPACT, IRRITATION AND YOUTHFUL OF ADDITION OF GLYCEROI OAHEXADECANETO FLUE·CURED QQAR~S REPOFII Na: T,243 18 May 1992 DISTRIBUTION: MI, G~A. Read Or. R,A, Baker 2 Mr. A,G, Stephenson 3 Dr, J,S, Wigand 4 Dr. J~S~ Wigand 5 Dr, P,J, Ounn 6 Dr, S,R, Massey 7 Prof. E, Rittershaw B Or, E, Kauseh 9 Dr, C.J~P, de Sigueira 10 Mr. E. Grant 11 Mr, H,V, thomsen 12 MI, f,l. Wilson 13 library 14 Library 15 Q 1992 BE Ca, u Dd POI COPYdlS~OPlld I~l~dbdid~d PL~IPT C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 Fundamental Research eentre, British·Ame~iean Tobacco Co, Ltd,, SOUTHAMPTON PCBICJSIBTM THE EFFECT ON IMPACT, IRRITATION AND MOUTHFUL OF ADDITION OF elYCEROL OR HE(ADECANE TO FLU~CURED CIGARETTES REPORT NO: T.243 18 May 1992 AUMORS; P,C, Bevan CJ, Shepperd PROJECT MANAGER: R,A, Crellin ISSUED BY: R,R, Baker COPY NO, Q I)P1BAT Co. Ird Oo not copy or rlwvwto ~ho~ld p~no~ O C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 Fundamental Research Centre, British American'fobaceo Co. Ltd., SOUTHAMPTON PCBICJSIBTM is May 1992 ~f~E EFFECT QN IMPACT, IRRlfA'flON AND MOUTHFUL OF ADDI'TION OF G1YQROL OR HU[ADECANE TD FLUE·CURED CIGARETTES REPORT NO~ T,243 SUMMARY: The sensation of impact is known to correlate wt the amount of e~traetable nicotine tie tree base nicotine) present in tobacco smoke, Thus smoke of higher pH will have greater impact even if the total amount of nicotine present is unchanged, It is not yet known for certain whether impact is mused by nicotine in the vapour phase or in the parfculate phase or both, but higher smoke pH will increase the proportion in the vapour phase, since the free base is more volatile than the protonated form of nicotine, However the release of nicotine into the vapour phase can be affected by factors other than the pH alone, since nicotine vapour pressure will depend on other aspects of the eomposlan of the smoke particles. Since smoke particles are composed of a large number of substances, ranging from water to waxes, some of which are mutually immiseible, the Chemical potential or "availability" of nicotine for transfer into the vapour phase could be anticipated to vary as the particle composition varied, with possible consequent changes in the impact sensation. It was therefore decided to test this hypothesis by a simple experiment involving the addition of two substances (giycerol and hexadecane~ to flue cured cigarettes and sensory assessment of the mainstream smoke for impact and irritation changes. These hM compounds were chosen to represent water·soluble and water·insoluble substances respecCvely~ No significant differences were found in the impact or initation scores for these cigarettes at the level of additives employed, indicating that there may be lit~ scape for modifying impact or irritation by altering the composition of smoke in this manner. In the ease of hexadecane, however, an increase in mouthful was observed. O 1992 BAT Co. ltd Do not copy pr shaw to unaut~tonsrd peaoir. C: I i I; PDF -!::!!::!!::!.f3 StlC.i: Dill No further work is planned in this area, INDEX TERMS: Sensory Assessment Impact Irritation Mouthful Glyeerol Hexadecane Flue·cured Tobacco Mainstream Smoke Smoke Chemical Properties Q 1991BAT Co, ltd Do oct copy or E~or,p uaauthorised p#xl~. · C Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 INTROOUCTTQN The sensation of impact obtainable from cigarette smoke is known to be caused by the nicotine present. Only the natural iswner of nicotine elicits impact (1), suggesting that a specific receptor type is involved. It is also known that the strength of the impact sensation correlates better with the amount of extractable nicotine present in smoke than with the total amount of nicotine present. This implies that 1 is the free base fcrn of nicotine which is more important in impact sensation, but it is not clear why Us should be the ease, One possibility is that the transport of nicotine tom smoke pa~tles to the impact receptors is via the MPMlr phase, and the vapour pressure of free base nicotine is of course higher than thatof the protonated form, Thus higher smoke pH leads to a greater proportion of nicotine present as the free base and perhaps therefore to a higher concentration of nicotine in the vapour phase, resulting in a more intense impact sensation, A second pnssibili~ is that it is the transport properties of tee base nicotine through the receptor membrane which make it more effective in inducing impact; free base nicotine is known to penetrate skin more rapidly(2,3). The receptor membrane may be lipophiiic (hydrophobic) in nature: the saliva layer which coats it is however aqueous, and its buffering capacity may also be relevant The situation is therefore complex The experiment described in this Report attempts to determine whether the impact properties of cigarette smoke can be modified by a simple adjustment of the balance of hydrophilic and hydrophobic substances in the smoke. / Smoke particles contain a mixture of substances ranging in pdarily tom water to long·chain hydrocarbon waxes, and are likely to be non· homogeneous in nature, Adjustment of the hydrophobielhydrophilic balance could affect either the vapour pressure of nicotine above the smoke particles by altering the partitioning of nicotine between the two phases in the particles, or could affect the access of nicotine to the receptor sites. In order to test this, a standard Aue·eured cigarette was injected with glyearol or with nhexadecane, to represent hydrophilic and hydrophobie materials respectively. The cigarettes were smoked, together with untreated controls, by a small panel, and were assessed for impact and other sensory attributes. MrmooS 1. CiParette.s~eetion and srenarati~ A laboratory standard Rue·cured cigarette (delivering 9 mg tar and ventilated to 40 1) was chosen far this study. Cigarettes were manually injected with either glyeed (15.4m9, or 2 x 25v1 of glyceml in ethanol (3008 mglmlJ) or n· hexadecane (20u1, or 15.409 (d30,7'1 at 200C)), These twocigarettes, along 6 1991BAT Co. tnd Do not copy or Ihow la uhwtbmised push, r3 C: I i I; PDF -!::!!::!!::!.f3 StlC.i: Dill I _ with the unspiked control, made up the three samples for this study. All cigarettes were stored under standard conditions of temperature and humidity far at least 48 hours prior to sensary testing. 2, Sensorv.lesti~a, A panel of seven smokers within FRC agreed to take part in this lest~ Each smoker was presented with an unspiked dgarette, a glyceml spiked cigarette and a questionaire, The panellists were asked to smoke the huo cigarettes together, and score for their impressions of impact, throat, mouth and nose irritationand mouthfull MI a 0·5 scale, using half integers as appropriate. On a separate occasion, the test was repeated · Us time comparing a conlml cigarette with one spiked wm n·hexadecane. The resulting data were analysed statistically using an analysis of variance, available on the SPSSX computer software package, RESULTIS, The results of the sensory assessments are eoliatedl for both tests, in Table TABLE 1 SENSORY DATA FOR GLYCEROL AND n·HEXADECANE SPII(ED CIGARETTES · COMPARED Wmt CONTROLS TEST 1 TEST 2 MM SCORES MEPN SCORES caeeet G~o~ [MI. (S,D.) CPnl Oie (S,O,) sp~ud Sg~eMe~. Headaran I SlgJlbnca IMPACT 178 J.W o·p '0·'8 257 2.9 O.Wh~P.II ~T~ROAT 3.07 2.89 "8' O·p 2.51 2.50 ~m~pa3 IRRITN, 021 a 0.11 MOUTH 1,86 2.07 a21'0·1' 214 1,93 IRRN. NOSE 2.71 2.92 on t o.la 29 236 O.TI~PP IRRITN. MOIIRC 2.42 2.70 0.36 t 0~ 286 28 0~3g~p.10 FUU N,S. = Cigarettes not significantly different (i,e, (901). Dl)aBUCIU DIMupy*iiar(oun~b.dpd C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 _ ~ ~C~ DISCIISSION The panellists found no signifiant diffe~ences b~een the glycerol spiked cigarettes and the controls for any of the sensory a~ibutes considered. They also deteded no differences in impd cc irritation be~een the n· hexadecane spiked and unspibd codol dgarenes. This was confirmed by comments made by be panellists, after completion of tie tests, The mouthful scores far this second test, however, inslcale significanUy increased mouthful sensations iorthe nhexadecane spiked cigaretes, eompred to the conbo~ The relevance of this one resu~ is unclear, particula~ in the light of La otter results presented in this report, and further tests would be required ~efore any strong conclusions can be drawn, The deliveries of g~erol and n·hexadeeane were not determined, given the lack of sensory differences found be~een the cigarettes. However, both additives are expected to have yansfered at around the 100k bevel. This should have been sufficient to reveal any changes in the sensory character resulting fmm Vie modification of the hydrophilidhydmphobic URce oflhe smoke. REFERENCES 1. B.kT, Report No. RD.218L 18.03,1991. 2. Oakley, D.M.; Swarbrick, J·~ Jpumal of Pharmacoicgiml Sdencas (1987), 76(12), 866871, 1 3. bungst, B.J.~ Ong Deve$menl and gdurli Pharmacy j19881, 14(11), 1481·1494, O 1991BhT Q. Ud Do na eapy olrhow~ ~mo~hori~d pmo~. C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111